The contents of all references, including articles, published patent applications and patents, if referred to anywhere in this specification are hereby incorporated by reference.
A large benefit of this sensor according to this invention, is that there can be several on a single wafer. It is a device able to measure chemical agent concentrations below part-per-billion (ppb) level and accurately determine the biomolecule agent and volume of biological cells present in human body. There is no device in the state-of-art, which allows concurrent detection of a chemical agent, biomolecule agent, and biological cell, all in a single system.
There are various kinds of sensor system. FIG. 1 shows a schematic representing the prior art of a sensor system 1 to detect biological cells, biomolecule agents or chemical agents (hereafter mentioned as specimen). The system 1 usually comprising with the sensor cell 2, power supply 4, detector 6, and analyzer 8. The system 1 usually detects or senses by detecting the electrical signal 10 induced due to absorption of the specimen. Detector 6 will detect the output signal 10 and send to the analyzer 8 to analyze the concentration of the specimen.
Several techniques can be found as the prior art for detecting concentration of specimen (common term used hereafter separately for chemical, biomolecule agents, or biological cells). However, most of them are based on the standard electrical technique wherein only single specimen is considered to detect. In addition, most technique requires long time in detection and/or not highly sensitive. The following, as a point of reference, are some methods, which are already patented and described as biosensors, used for detection of biological cells.
Peeters, in U.S. Pat. No. 6,325,904, (issued on Dec. 4, 2001), discloses a nanosensor, using an array of electrodes at the atomic or nano scale (nanoelectrodes) level, formed by using specific receptors. Utilizing the level of current flow while specific biological cells attached determine the concentration. The drawbacks of such technique are: (i) requiring STM to position the receptor which time consuming fabricating such sensor, (ii) requiring specific nano-scale level gap in between electrodes containing receptor to conduct current, (iii) difficulties in measuring low current level (corresponding to low concentration) due to use of computer controlled technique, and (iv) requiring high power due to using of computer controlled signal processing.
Bornhop, et al., in U.S. Pat. No. 6,809,828, (issued Oct. 26, 2004), discloses an sensor system for detecting proteins or DNA. Concentration is estimated based on the fringe pattern, detected by the CCD camera in addition with laser beam analyzer. Fringe pattern is usually depending on the laser intensity and position of the CCD camera. The drawback of this technique are, (i) in accuracy in concentration measurement as fringe pattern is dependent on the laser intensity and position, (ii) difficulties in low level concentration measurement due to difficulties in finding small changes in fringe pattern, and (iii) complete system becoming bulky as CCD camera, position sensor, and laser beam analyzer are to be used.
Britton, Jr., et al., in U.S. Pat. No. 6,167,748, (issued Jan. 2, 2001), discloses a technique for detecting the glucose concentration in blood. Measurement of concentration is performed based on standard technique of measuring the changes in capacitance. Technique uses cantilever coated with the receptor for absorbing the glucose. Main drawbacks are: (i) inability to detect low level concentration as very low changes in the capacitive is difficult to measure, and (ii) difficulties of detection of different kind of biological cell at the same time as each cantilever require different coating. Similar detection techniques can also be found in other patents such as U.S. Pat. No. 6,856,125, of Kermani (issued Feb. 15, 2005), U.S. Pat. No. 5,798,031 Charlton et al., (issued Aug. 25, 1998), U.S. Pat. No. 5,264,103 of Yoshioka et. al., (issued Nov. 23, 1993), and U.S. Pat. No. 5,120,420 of Nankai et. al., (issued Jun. 9, 1992), in all of which capacitive techniques are used to detect the concentration. Chemical and biological sensors can be miniaturized using nanowires or carbon nanotubes. Continued advances in nanoscience and nanotechnology require tiny sensors and devices to analyze small sample sizes. The following is a discussion of the prior art in sensor fabrication.
After discussing the above issues pertaining to the state-of-art biosensors, chemical sensors, and biomolecule sensors, and methods of making them, we would now like to introduce a novel technique where multiple chemical agents can concurrently be detected in real time and the information can quickly be transmitted to a main station and displayed. It is small in size, so the end user may carry it anywhere to measure the biological cell volume, protein, and biomolecule cells in a medical science application and is also able to do concurrent real time detection of different kinds of chemical agents.
Despite the advances in therapeutics and improved public health measures, infectious diseases still remain the major cause of morbidity and mortality in most parts of the world. Clinical syndromes are rarely specific for single pathogens, so multiplexed diagnostics provide good detection sensitivity, but are often slow, bulky, expensive, and reliant on trained medical personnel. The development of handheld diagnostic systems that can provide rapid diagnosis for multiplexed detection of pathogens could significantly contribute to the prevention and treatment of infectious diseases.
Similarly, that same multiplexed detection technology can be utilized to diagnose a single condition, such as HIV. Studies have shown that people newly infected with HIV are most contagious because of the initial high viral loads. However, early stage detection is currently expensive and inaccurate. These detection systems have proven to be of limited benefit. Many potentially infected people cannot afford the laboratory testing necessary, or cannot justify the cost due to the chances of a misdiagnosis. The multiplexed sensor described herein, however, will be relatively inexpensive, can be used by the average consumer, and will give results quickly and accurately. There is thus a corresponding need to develop a universal diagnosis device, which can diagnosis multiple bio-agents (including infectious diseases, cells, DNA, RNA etc.), improve the effectiveness, sensitivity, and accuracy of diagnosis by reducing time and complexity, and by improving accuracy and consistency of assessment of diagnosis studies. There is a clear role and need for a system and methods, to improve sensitivity, accuracy, and diagnosis time and facilitate more accurate and consistent diagnosis.